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1. 发明申请

WO2010045241A1 BIODEGRADABLE PROLINE-BASED POLYMERS 审中-公开
标题翻译：生物可降解的基于聚合物的聚合物
公开(公告)号：WO2010045241A1
公开(公告)日：2010-04-22
申请号：PCT/US2009/060521
申请日：2009-10-13
申请人： MEDIVAS, LLC , TURNELL, William, G. , GOMURASHVILI, Zaza, D. , ANDERL, Jeffrey, Neil
发明人： TURNELL, William, G. , GOMURASHVILI, Zaza, D. , ANDERL, Jeffrey, Neil
IPC分类号： A61L15/16
CPC分类号： A61K9/5153 , A61K31/00 , C08G69/44 , C08L77/12
摘要： The invention provides sequential poly(ester amide)s derived from Proline and that are synthesized by a two-step method, involving a final thermal polyesterification reaction. Molecular weights of polymers prepared by this method are from 14,000 Da to about 77,000Da.l When invention proline-based PEAs were thermally characterized,, their glass transition temperatures were lower than other alpha-amino acid based poly(ester amides) due to lack of internal hydrogen bonding. These Proline-based PEAs assemble as nano-particles in aqueous solutions and form complexes with various cations and biologies, including hydrophobic small molecule drugs and biologies. Therefore the invention Proline- based PEAs are useful for drug delivery applications requiring a polymer with a molecular weight in the range from 14,000 Da to about 77,000Da and for fabrication of nanoparticles for delivery of hydrophobic drugs.
摘要翻译：本发明提供了源自脯氨酸的顺序聚（酯酰胺），并且通过两步法合成，涉及最终的热聚酯化反应。通过该方法制备的聚合物的分子量为14,000Da至约77,000Da。当本发明的脯氨酸基PEA被热表征时，由于缺乏，其玻璃化转变温度低于其它基于α-氨基酸的聚（酯酰胺）的内部氢键。这些基于脯氨酸的PEAs在水溶液中作为纳米颗粒组装，并与各种阳离子和生物制品形成复合物，包括疏水性小分子药物和生物制剂。因此，本发明的基于脯氨酸的PEAs可用于需要分子量范围为14,000Da至约77,000Da的聚合物并用于制备用于递送疏水性药物的纳米颗粒的药物递送应用。

2. 发明申请

WO2006088647A1 POLYMER PARTICLE DELIVERY COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：聚合物颗粒递送组合物和使用方法
公开(公告)号：WO2006088647A1
公开(公告)日：2006-08-24
申请号：PCT/US2006/003575
申请日：2006-01-31
申请人： MEDIVAS, LLC , TURNELL, William, G. , LI, Hong , GOMURASHVILI, Zaza, D. , HUGHES, Jonathan, Macferran , DA, Jie , ZHANG, Huashi , KATSARAVA, Ramaz
发明人： TURNELL, William, G. , LI, Hong , GOMURASHVILI, Zaza, D. , HUGHES, Jonathan, Macferran , DA, Jie , ZHANG, Huashi , KATSARAVA, Ramaz
IPC分类号： A61K9/50
CPC分类号： A61K9/1075 , A61K9/1647 , A61K9/5031 , A61K9/5153 , A61K47/34 , A61K47/59 , A61K47/593 , A61K47/595 , C07K16/2821 , C08L77/12 , C12N15/88
摘要： The present invention provides biodegradable polymer particle delivery compositions based on polymers, such as polyester amide (PEA) and polyester urethane (PEUR) polymers, that contain amino acids in the polymer. The polymer particle delivery compositions can be formulated as a liquid dispersion of polymer particles with the bioactive agents dispersed in the particle or conjugated attached to polymer molecules or particle surfaces. The bioactive agents can include drugs, polypeptides, DNA and cells for cell-based therapies using particles sized for local, mucosal or circulatory delivery. Methods of treating a disease by administering to a subject the polymer particle delivery composition, which incorporates a bioactive agent suitable for treatment of the disease, or its symptoms, are also included.
摘要翻译：本发明提供了基于在聚合物中含有氨基酸的聚合物如聚酯酰胺（PEA）和聚酯聚氨酯（PEUR）聚合物的可生物降解的聚合物颗粒递送组合物。聚合物颗粒递送组合物可以配制成聚合物颗粒的液体分散体，其中分散在颗粒中的生物活性剂或缀合在聚合物分子或颗粒表面上。生物活性剂可以包括药物，多肽，DNA和细胞用于基于细胞的疗法，使用尺寸适合局部，粘膜或循环递送的颗粒。还包括通过向受试者施用包含适合于治疗该疾病的生物活性剂的聚合物颗粒递送组合物或其症状来治疗疾病的方法。

3. 发明申请

WO2009137711A1 BIODEGRADABLE METAL-CHELATING POLYMERS AND VACCINES 审中-公开
标题翻译：生物可降解金属螯合聚合物和疫苗
公开(公告)号：WO2009137711A1
公开(公告)日：2009-11-12
申请号：PCT/US2009/043192
申请日：2009-05-07
申请人： MEDIVAS, LLC , TURNELL, William, G. , GOMURASHVILI, Zaza, D. , PARCHER, Benjamin, W. , HUGHES, Jonathan , ANDERL, Jeffrey, N.
发明人： TURNELL, William, G. , GOMURASHVILI, Zaza, D. , PARCHER, Benjamin, W. , HUGHES, Jonathan , ANDERL, Jeffrey, N.
IPC分类号： A61M37/00 , C08F283/04
CPC分类号： C08F283/04 , A61K47/593 , A61K47/595 , A61K47/60 , A61K47/6935 , A61K49/0047 , A61K49/0093 , A61K49/128 , C08G69/44 , C08G73/028 , C08L77/12 , C08L79/02
摘要： The invention provides metal-chelating poly (ether amide) polymers useful in preparation of polymer compositions for delivering a variety of cargo molecules, such as bioactive agents. In solution metal ions and cargo molecules, such as vaccine epitopes, that include metal avid amino acids can be loaded into the polymer compositions and held in a non-covalent complex. Nanoparticles of such polymer compositions can also be prepared directly from the solution.
摘要翻译：本发明提供了可用于制备用于递送各种货物分子的生物活性剂的聚合物组合物的金属螯合聚（醚酰胺）聚合物。在溶液中，金属离子和货物分子，如疫苗表位，包括金属氨基酸，可加载到聚合物组合物中并保持在非共价复合物中。这种聚合物组合物的纳米颗粒也可以直接从溶液制备。

4. 发明申请

WO2009026543A3 CATIONIC ALPHA-AMINO ACID-CONTAINING BIODEGRADABLE POLYMER GENE TRANSFER COMPOSITIONS 审中-公开
公开(公告)号：WO2009026543A3
公开(公告)日：2009-02-26
申请号：PCT/US2008/074069
申请日：2008-08-22
申请人： MEDIVAS, LLC , TURNELL, William, G. , CRUZ-ARANDA, Gina, Ann , WU, Mark, Minzhi , CHANTUNG, Ronald, Lee , GOMURASHVILI, Zaza, D. , DEFIFE, Kristin, M.
发明人： TURNELL, William, G. , CRUZ-ARANDA, Gina, Ann , WU, Mark, Minzhi , CHANTUNG, Ronald, Lee , GOMURASHVILI, Zaza, D. , DEFIFE, Kristin, M.
IPC分类号： C08G63/48
摘要： The invention provides gene transfer compositions using as the gene carrier a biodegradable polymer that contains one or more cationic alpha amino acids, such as argininc or agmatine. The compositions form a tight soluble complex with a poly nucleic acid suitable for transfecting target cells to effect translation of the cargo poly nucleic acid by the target cell. Thus, such compounds are useful both in vitro and in vivo.

5. 发明申请

WO2006132950A2 THERAPEUTIC POLYMERS AND METHODS OF USE 审中-公开
标题翻译：治疗性聚合物及其使用方法
公开(公告)号：WO2006132950A2
公开(公告)日：2006-12-14
申请号：PCT/US2006/021395
申请日：2006-06-02
申请人： MEDIVAS, LLC , TURNELL, William, G. , GOMURASHVILI, Zaza, D. , KATSARAVA, Ramaz
发明人： TURNELL, William, G. , GOMURASHVILI, Zaza, D. , KATSARAVA, Ramaz
IPC分类号： A61K48/00 , A61K31/785
CPC分类号： A61K48/0041 , A61K31/785 , A61K47/58 , A61K47/59 , A61K47/593 , A61K47/595 , C08G71/04 , C08L77/12
摘要： The present invention provides biodegradable therapeutic polymer compositions based on poly(ester amide) (PEA), poly(ester urethane) (PEUR), and poly(ester urea) (PEU) polymers useful for in vivo delivery of at least one therapeutic diol or di-acid incorporated into the backbone of the biodegradable polymer. The therapeutic polymer compositions biodegrade in vivo by enzymatic action to release therapeutic diols or di-acids from the polymer backbone in a controlled manner over time. The invention compositions are stable, can be lyophilized for transportation and storage, and can be redispersed for administration. Due to structural properties of the PEA and PEUR polymers used, the invention therapeutic polymer compositions provide for high loading of the therapeutic diol or di-acid, as well as optional bioactive agents.
摘要翻译：本发明提供了可用于体内递送至少一种治疗性二醇的聚（酯酰胺）（PEA），聚（酯聚氨酯）（PEUR）和聚（酯尿素）（PEU）聚合物的可生物降解的治疗性聚合物组合物，二酸掺入可生物降解聚合物的骨架中。治疗性聚合物组合物通过酶作用在体内生物降解，以随时间的控制方式从聚合物主链释放治疗性二醇或二酸。本发明组合物是稳定的，可以冻干运输和储存，并且可以再分散用于给药。由于所使用的PEA和PEUR聚合物的结构性质，本发明的治疗性聚合物组合物提供治疗性二醇或二酸的高负载量以及任选的生物活性剂。

6. 发明申请

WO2009073814A2 OLIGO-ETHYLENE GLYCOL-BASED POLYMER COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：低聚乙二醇基聚合物组合物及其使用方法
公开(公告)号：WO2009073814A2
公开(公告)日：2009-06-11
申请号：PCT/US2008/085583
申请日：2008-12-04
申请人： MEDIVAS, LLC , CORNELL UNIVERSITY , CHU, Chih-Chang , KATSARAVA, Ramaz , GOMURASHVILI, Zaza, D. , TURNELL, William, G.
发明人： CHU, Chih-Chang , KATSARAVA, Ramaz , GOMURASHVILI, Zaza, D. , TURNELL, William, G.
IPC分类号： A61K9/14
CPC分类号： A61K47/34 , A61K9/0024 , C08G69/40 , C08G69/44 , C08G71/04 , C08G2230/00 , C08K5/0008 , C08L77/06 , C08L77/12
摘要： The invention provides biodegradable PEAs, PEURs and PEUs that are synthesized by solution polycondensation to include α-amino acids and oligo-ethylene ether segments in the polymer backbone. The polymers can be obtained by substituting oligo- ethylene glycol (OEG) for aliphatic di-acid and diols during their fabrication. Also provided are compositions in which bioactive agents are dispersed in the polymers. The compositions biodegrade by enzymatic action to release incorporated bioactive agents and oligo-ethylene glycol segments, which are fully biodegradable at a molecular weight less than 400 Da,. Due to their comparatively rapid surface enzymatic hydrolysis, the compositions can be used to deliver bioactive agents in a controlled manner within a relatively rapid delivery time, such as about 18 to 24 hours.
摘要翻译：本发明提供可生物降解的PEA，PEUR和PEU，其通过溶液缩聚合成以在聚合物骨架中包含α-氨基酸和低聚乙烯醚链段。聚合物可以通过在制造过程中用低聚乙二醇（OEG）取代脂肪族二酸和二醇来获得。还提供了生物活性剂分散在聚合物中的组合物。该组合物通过酶促作用生物降解以释放掺入的生物活性剂和低聚乙二醇片段，其在低于400Da的分子量下完全可生物降解。由于它们相对快速的表面酶水解，所述组合物可以用于在相对较快的传送时间内（例如约18至24小时）以受控方式传送生物活性剂。

7. 发明申请

WO2010019716A1 AABB-POLY(DEPSIPEPTIDE) BIODEGRADABLE POLYMERS AND METHODS OF USE 审中-公开
标题翻译： AABB-POLY（DEPSIPEPTIDE）可生物降解的聚合物及其使用方法
公开(公告)号：WO2010019716A1
公开(公告)日：2010-02-18
申请号：PCT/US2009/053618
申请日：2009-08-12
申请人： MEDIVAS, LLC , KATSARAVA, Ramaz , OCHKHIKIDZE, Natia , TUGUSHI, David , GOMURASHVILI, Zaza, D.
发明人： KATSARAVA, Ramaz , OCHKHIKIDZE, Natia , TUGUSHI, David , GOMURASHVILI, Zaza, D.
IPC分类号： A61K31/785
CPC分类号： A61K31/785 , C08G69/44 , C08L77/12
摘要： The invention provides AABB-poly(depsipeptide)s (AABB-PDPs), a class of biodegradable polymers composed of α-amino and α-hydroxy acids with material properties suitable for biomedical applications. These AABB-PDPs belong to the family of amino acid- based poly(ester amide)s (PEAs), which are characterized by the presence of alternating ester and amide functionalities. Containing four ether groups per basic unit, these polymers degrade rapidly by biotic or abiotic hydrolytic action to release dispersed bioactive agents at a controlled delivery rate, are non-toxic, produce digestible breakdown products, and are easy to fabricate by solution polycondensation.
摘要翻译：本发明提供了一种由α-氨基和α-羟基酸组成的一类可生物降解的聚合物（AABB-PDPs），其具有适用于生物医学应用的材料性质。这些AABB-PDP属于基于氨基酸的聚（酯酰胺）（PEAs）家族，其特征在于存在交替的酯和酰胺官能团。每个基本单位含有四个醚基团，这些聚合物通过生物或非生物水解作用快速降解，以受控的输送速率释放分散的生物活性剂，是无毒的，产生可消化的分解产物，并且易于通过溶液缩聚制备。

8. 发明申请

WO2009015143A1 BIODEGRADABLE CATIONIC POLYMER GENE TRANSFER COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：生物可降解阳离子聚合物基因转移组合物和使用方法
公开(公告)号：WO2009015143A1
公开(公告)日：2009-01-29
申请号：PCT/US2008/070759
申请日：2008-07-22
申请人： MEDIVAS, LLC , CORNELL UNIVERSITY , CHU, Chih-chang , MUTSCHLER-CHU, Martha, A. , SONG, Hua , LIU, Bo , GOMURASHVILI, Zaza, D.
发明人： CHU, Chih-chang , MUTSCHLER-CHU, Martha, A. , SONG, Hua , LIU, Bo , GOMURASHVILI, Zaza, D.
IPC分类号： C08G63/00 , C12N15/00
CPC分类号： C08L77/12 , C08G2230/00 , C08L75/06 , C12N15/87 , C12N15/88
摘要： The invention provides biodegradable, cationic compositions based on cationic α-amino acid-containing PEA, PEUR and PEU polymers for use in preparation of non-viral gene transfer compositions. In the invention gene transfer compositions a poly nucleic acid is condensed with the polymer to form a soluble unit wherein the electrical charge of the poly nucleic acid is neutralized by the polymers. The invention gene transfer compositions can be used to transfect target cells by contact with the target cells.
摘要翻译：本发明提供了基于含有阳离子α-氨基酸的PEA，PEUR和PEU聚合物的可生物降解阳离子组合物，用于制备非病毒基因转移组合物。在本发明的基因转移组合物中，聚核酸与聚合物缩合形成可溶性单元，其中多核酸的电荷被聚合物中和。本发明的基因转移组合物可用于通过与靶细胞接触来转染靶细胞。

9. 发明申请

WO2009011938A1 BIOABSORBABLE ELASTOMERIC ARTERIAL SUPPORT DEVICE AND METHODS OF USE 审中-公开
标题翻译：生物可塑性弹性体支架装置及其使用方法
公开(公告)号：WO2009011938A1
公开(公告)日：2009-01-22
申请号：PCT/US2008/058785
申请日：2008-03-28
申请人： MEDIVAS, LLC , GOMURASHVILI, Zaza, D. , CARPENTER, Kenneth, W.
发明人： GOMURASHVILI, Zaza, D. , CARPENTER, Kenneth, W.
IPC分类号： A61K31/74 , A61F2/00
CPC分类号： A61L31/148 , A61K47/6957 , A61L31/06 , A61L31/146 , C08L77/12
摘要： The invention provides bioabsorbable elastomeric arterial support devices fabricated using elastomeric polymer networks and semi-interpenetrating networks in which a linear polymer is crosslinked by ester or alpha-amino-acid containing cross-linkers that polymerize upon exposure to active species. The invention devices are designed for implant into curved segments of artery and can be expanded during arterial implant and cross-linked in vivo in the expanded state to restore a clogged artery to extended function. The invention devices are useful for in vivo implant in diseased arteries and for delivery of a variety of therapeutic molecules in a time release fashion to surrounding tissues to reduce or eliminate arterial response to implant of the device.
摘要翻译：本发明提供使用弹性体聚合物网络和半互穿网络制造的生物可吸收弹性体动脉支持装置，其中线性聚合物通过酯或含有α-氨基酸的交联剂在暴露于活性物质时聚合而交联。本发明装置被设计用于植入到动脉的弯曲部分中，并且可以在动脉植入期间扩张并且在膨胀状态下在体内交联以将阻塞的动脉恢复到延伸的功能。本发明装置可用于在患病动脉中的体内植入以及以时间释放方式将各种治疗分子递送至周围组织以减少或消除对装置植入的动脉反应。

10. 发明申请

WO2007050415A2 POLY(ESTER UREA) POLYMERS AND METHODS OF USE 审中-公开
标题翻译： POLY（ESTER UREA）POLYMERS AND METHODS OF USE
公开(公告)号：WO2007050415A2
公开(公告)日：2007-05-03
申请号：PCT/US2006/040825
申请日：2006-10-19
申请人： MEDIVAS, LLC , KATSARAVA, Ramaz , TUGUSHI, David , GOMURASHVILI, Zaza, D.
发明人： KATSARAVA, Ramaz , TUGUSHI, David , GOMURASHVILI, Zaza, D.
IPC分类号： A61K31/56 , C08F20/00 , A61F2/02
CPC分类号： A61K31/56 , A61L27/18 , A61L31/06 , C08G71/04 , C08G2230/00 , C08G2250/00 , C08L75/02
摘要： The invention provides high molecular weight, crystalline or semi crystalline biodegradable and biocompatible poly(ester urea) (PEU) polymers useful for making vascular stents and hard tissue replacement implants, such as bone substitutes. The PE polymers are based on α amino acids and are made by a polycondensation reaction. PE polymer compositions can contain a therapeutic diol incorporated into the polymer backbone that is released from such an implant in situ. Bioactive agents, such as analgesics, antibiotics, and the like, can also be covalently attached to certain PEU polymers for release into tissue surrounding an implant during biodegradation of the polymer.
摘要翻译：本发明提供了可用于制备血管支架和硬组织置换植入物例如骨代用品的高分子量，结晶或半结晶可生物降解和生物相容的聚（酯尿素）（PEU）聚合物。 PE聚合物基于氨基酸，并通过缩聚反应制备。 PE聚合物组合物可以含有掺入到聚合物骨架中的治疗性二醇，其从原位从这种植入物中释放出来。生物活性剂，例如止痛剂，抗生素等也可以共价连接到某些PEU聚合物，以在聚合物的生物降解过程中释放到植入物周围的组织中。

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